Antigen presentation by macrophages is enhanced by the uptake of necrotic, but not apoptotic, cells

Clinical and Experimental Immunology - Tập 127 Số 2 - Trang 220-225 - 2002
Robert N. Barker, L-P Erwig, Kathryn Hill1, Anne Devine1, Wayne Pearce1, Andrew J. Rees1
1Department of Medicine and Therapeutics, University of Aberdeen, UK

Tóm tắt

SummaryThe aim of this study was to determine whether phagocytosis of necrotic or apoptotic cells affects antigen presentation by murine bone marrow-derived macrophages. After uptake of necrotic neutrophils, macrophages were able to stimulate significantly higher T cell proliferation in vitro against both the recall antigen albumin and the mitogen concanavalin A. No such effect was seen following phagocytosis of apoptotic neutrophils. Flow cytometry revealed that, within 4h of ingestion, macrophages that had taken up the necrotic cells expressed higher levels of CD40 than those that had phagocytosed apoptotic cells. Macrophage cultures pulsed with apoptotic, but not necrotic, neutrophils contained higher levels of transforming growth factor β1, but lower concentrations of tumour necrosis factor α, compared to untreated controls. Our interpretation of these results is that macrophages that have taken up necrotic neutrophils co-stimulate T cells with greater efficiency due to rapid CD40 up-regulation, whereas those that have ingested apoptotic cells are not only ineffective in co-stimulation, but also secrete inhibitory cytokine.

Từ khóa


Tài liệu tham khảo

Matzinger, 1994, Tolerance, danger and the extended family., Ann Rev Immunol, 12, 991, 10.1146/annurev.iy.12.040194.005015

Gallucci, 1999, Natural adjuvants: endogenous activators of dendritic cells., Nature Med, 5, 1249, 10.1038/15200

Fearon, 1996, The instructive role of innate immunity in the acquired immune response., Science, 272, 50, 10.1126/science.272.5258.50

Janeway, 1998, The road less travelled by. The role of innate immunity in the adaptive immune response., J Immunol, 161, 539

Vandenbark, 1985, Specificity of T lymphocytes lines for peptides of myelin basic protein., J Immunol, 135, 229, 10.4049/jimmunol.135.1.229

Hooper, 1987, Self-tolerance for erythrocytes is not maintained by clonal deletion of T helper cells., Immunol Today, 8, 327330, 10.1016/0167-5699(87)90005-3

Elson, 1995, Immunologically ignorant autoreactive T cells, epitope spreading and repertoire limitation., Immunol Today, 16, 71, 10.1016/0167-5699(95)80091-3

DiPietro, 1998, MIP-1alpha as a critical macrophage chemoattractant in murine wound repair., J Clin Invest, 101, 1693, 10.1172/JCI1020

Adams, 1998, Macrophages as destructive cells in host defence., Inflammation: basic principles and clinical correlates, 471

North, 1978, The concept of the activated macrophage., J Immunol, 121, 806, 10.4049/jimmunol.121.3.806

Murray, 1988, Interferon-gamma, the activated macrophage, the host defence against microbial challenge., Ann Inter Med, 108, 595, 10.7326/0003-4819-108-4-595

Goerdt, 1999, Other functions, other genes: alternative activation of antigen-presenting cells., Immunity, 10, 137, 10.1016/S1074-7613(00)80014-X

Erwig, 1998, Initial cytokine exposure determines macrophages’ function and renders them unresponsive to other cytokines., J Immunol, 161, 1983, 10.4049/jimmunol.161.4.1983

Erwig, 2000, Systemic IL-4 treatment does not alter macrophage programming but modulates macrophage function within nephritic glomeruli., Am J Path, 156, 295, 10.1016/S0002-9440(10)64730-X

Reiter, 1999, Differential effect of apoptotic versus necrotic tumor cells on macrophage antitumor activities., J Immunol, 163, 1730, 10.4049/jimmunol.163.4.1730

Meagher, 1992, Phagocytosis of apoptotic neutrophils does not induce release of thromboxane B2., J Leukoc Biol, 52, 269, 10.1002/jlb.52.3.269

Fadok, 2001, Differential effects of apoptotic versus lysed cells on macrophage production of cytokines: role of proteases., J Immunol, 166, 6847, 10.4049/jimmunol.166.11.6847

Fadok, 1998, Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2 and PAF., J Clin Invest, 101, 890, 10.1172/JCI1112

McDonald, 1999, Transcriptional and translational regulation of inflammatory mediator production by endogenous TGF-β in macrophages that have ingested apoptotic cells., J Immunol, 163, 6164, 10.4049/jimmunol.163.11.6164

Erwig, 1999, Previous uptake of apoptotic neutrophils or ligation of integrin receptors downmodulates the ability of macrophages to ingest apoptotic neutrophils., Blood, 93, 1406, 10.1182/blood.V93.4.1406

Perry, 1996, Autoreactive T cell specificity in autoimmune hemolytic anemia of the NZB mouse., Eur J Immunol, 26, 136, 10.1002/eji.1830260121

Savill, 1989, Macrophage phagocytosis of ageing neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition of macrophages., J Clin Invest, 83, 865, 10.1172/JCI113970

Durie, 1994, The role of CD40 in the regulation of humoral and cell-mediated immunity., Immunol Today, 15

June, 1994, The B7 and CD28 receptor families., Immunol Today, 15, 321, 10.1016/0167-5699(94)90080-9

Letterio, 1997, TGF-β: a critical modulator of immune cell function., Clin Immunol Immunopathol, 84, 244, 10.1006/clin.1997.4409